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hot flash; menopausal vasomotor symptom

Etiology: 1) menopause 2) treatment of breast cancer 3) treatment of prostate cancer Epidemiology: - longer duration of symptoms in black women - shorter duration of symptoms in obese women Pathology: - vasomotor symptoms - hypothalamic neurokinin B & its receptor, NK3R, may play a role in the etiology of hot flashes [18] Clinical manifestations: - symptoms exacerbated by depression [8] - duration of moderate-to-severe hot flashes: - mean duration 5.5 years [9]; 7.4 years [14]; 10.2 years [10] - effects on objective vs subjective sleep disturbance differ [11] Complications: - women with untreated vasomotor symptoms use more outpatient healthcare services & lose more work days than symptom-free women [15] Management: 1) estrogen is 1st line agent for menopausal hot flashes - estrogen + progestin unless hysterectomy - see hormone replacement therapy 2) Megace 20 mg PO BID 3) venlafaxine (Effexor): start 12.5 mg PO BID - as effective as estrogen [12,13] 4) serotonin re-uptake) inhibitors (SSRI) [4,5] a) paroxetine CR (Paxil) 7.5-25 mg PO QD [4] - may be effective & an acceptable alternative to hormone replacement [4] b) fluxoetine (Prozac) 20 mg PO QD of no benefit c) Zoloft 25-50 mg PO QD d) citalopram of no benefit [5] 5) orally active neurokinin B antagonist (MLE4901) reduces frequency & severity of hot flashes [18] 6) fezolinetant a neurokinin-3 receptor antagonist (FDA-approved 2023) - 30mg & 45mg fezolinetant improved menopausal quality of life at 12 weeks [24] 7) gabapentin (Neurontin): start 100 mg PO QHS 8) clonidine, Catapres TTS, 0.1-0.3 mg/day [2,3] 9) fennel may be of benefit for menopausal symptoms [19] 10) exercise may benefit women with depression [8] 11) soy protein of no benefit [5] 12) acupuncture of no value [16] 13) cognitive behavioral therapy for insomnia [20] - mindfulness training, cognitive behavioral therapy, & behavior-based therapy helpful in relieving hot-flashes [21]

Related

hormone replacement therapy (HRT); estrogen replacement therapy; postmenopausal hormone replacement therapy menopause

General

sign/symptom

References

  1. Prescriber's Letter 7(8):44 2000
  2. Greendale G, UCLA Women's Health Center, personal communication
  3. Prescriber's Letter 10(6):34 2003
  4. NEJM Knowledge+ - Journal Watch 23(14):112, 2003 Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003 Jun 4;289(21):2827-34. PMID: 12783913
  5. Journal Watch 25(5):40-41, 2005 Suvanto-Luukkonen E, Koivunen R, Sundstrom H, Bloigu R, Karjalainen E, Haiva-Mallinen L, Tapanainen JS. Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo- controlled, double-blind study. Menopause. 2005 Jan-Feb;12(1):18-26. PMID: 15668596 - Kok L, Kreijkamp-Kaspers S, Grobbee DE, Lampe JW, van der Schouw YT. A randomized, placebo-controlled trial on the effects of soy protein containing isoflavones on quality of life in postmenopausal women. Menopause. 2005 Jan-Feb;12(1):56-62. PMID
  6. Nelson HD et al, Nonhormonal therpies for postmenopausal hot flashes: Systematic review and meta-analysis. JAMA 2006; 295:2057 PMID: 16670414 - Tice JA and Grady D Alternatice to estrogne for treatment of hot flashes: Are they effective and safe? JAMA 2006; 295:2076 PMID: 16670417
  7. Reddy SY et al, Gabapentin, estrogen and placebo for treating hot flushes: A randomized controlled trial. Obstet Gynecol 2006; 108:41 PMID: 16816054
  8. Thurston RC et al, Physical activity and risk of vasomotor symptoms in women with and without a history of depression: Results from the Harvard Study of Moods and Cycles. Menopause 2006, 13:553 PMID: 16837876
  9. Col NF et al. Duration of vasomotor symptoms in middle-aged women: A longitudinal study. Menopause 2009 May/Jun; 16:453.
  10. Freeman EW et al. Duration of menopausal hot flushes and associated risk factors. Obstet Gynecol 2011 May; 117:1095. PMID: 21508748
  11. Thurston RC et al. Are vasomotor symptoms associated with sleep characteristics among symptomatic midlife women? Comparisons of self-report and objective measures. Menopause 2012 Jul; 19:742 PMID: 22415568 - Regestein QR. Do hot flashes disturb sleep? Menopause 2012 Jul; 19:715 PMID: 22735095
  12. Joffe H et al Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor SymptomsA Randomized Clinical Trial. JAMA Intern Med. Published online May 26, 2014 PMID: 24861828 http://archinte.jamanetwork.com/article.aspx?articleid=1876676
  13. Reed SD et al. Sexual function in women on estradiol or venlafaxine for hot flushes: A randomized controlled trial. Obstet Gynecol 2014 Aug; 124:233 PMID: 25004335
  14. Avis NE et al Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Intern Med. JAMA Intern Med. 2015;175:531-539 PMID: 25686030 http://archinte.jamanetwork.com/article.aspx?articleid=2110996 - Richard-Davis G, Manson JE Vasomotor Symptom Duration in Midlife Women-Research Overturns Dogma. JAMA Intern Med. Published online February 16, 2015 PMID: 25686269 http://archinte.jamanetwork.com/article.aspx?articleid=2110993
  15. Judge DE The High Cost of Hot Flashes. NEJM Journal Watch. March 10 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Sarrel P et al. Incremental direct and indirect costs of untreated vasomotor symptoms. Menopause 2015 Mar; 22:260. PMID: 25714236 - Pinkerton JV. Money talks: Untreated hot flashes cost women, the workplace, and society. Menopause 2015 Mar; 22:254. PMID: 25692878
  16. Ee C, Xue S, Chondros P et al Acupuncture for Menopausal Hot Flashes: A Randomized Trial. Ann Intern Med. Published online 19 January 2016 http://annals.org/article.aspx?articleid=2481811
  17. Imai A, Matsunami K, Takagi H, Ichigo S. New generation nonhormonal management for hot flashes. Gynecol Endocrinol. 2013 Jan;29(1):63-6. Review. PMID: 22809093
  18. Prague JK, Roberts RE, Comninos AN et al. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: A phase 2, randomised, double-blind, placebo-controlled trial. Lancet 2017 Apr 3; PMID: 28385352 Free Article http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30823-1/fulltext - Sassarini J, Anderson RA. New pathways in the treatment for menopausal hot flushes. Lancet 2017 Apr 3 PMID: 28385351 Free full text http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30886-3/fulltext
  19. Rahimikian F, Rahimi R, Golzareh P, Bekhradi R, Mehran A. Effect of Foeniculum vulgare Mill. (fennel) on menopausal symptoms in postmenopausal women: a randomized, triple-blind, placebo-controlled trial. Menopause. May 15, 2017 PMID: 28509813 http://journals.lww.com/menopausejournal/Abstract/publishahead/Effect_of_Foeniculum_vulgare_Mill___fennel__on.97782.aspx
  20. Guthrie KA, Larson JC, Ensrud KE et al. Effects of pharmacologic and nonpharmacologic interventions on insomnia symptoms and subjective sleep quality in women with hot flashes: A pooled analysis of individual participant data from 4 MsFLASH trials. Sleep 2017 Nov 20 PMID: 29165623 https://academic.oup.com/sleep/advance-article-abstract/doi/10.1093/sleep/zsx190/4642822?redirectedFrom=fulltext
  21. van Driel C, Stuursma AS, Schroevers MJ, Mourits M, de Bock GH. Mindfulness, cognitive behavioural and behaviour-based therapy for natural and treatment-induced menopausal symptoms: A systematic review and meta-analysis. BJOG 2018 Mar 15 PMID: 29542222
  22. Medical Knowledge Self Assessment Program (MKSAP) 18, American College of Physicians, Philadelphia 2018
  23. Fraser GL, Lederman S, Waldbaum A et al. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause 2020 Apr; 27:382 PMID: 32102086 Free PMC Article https://journals.lww.com/menopausejournal/FullText/2020/04000/A_phase_2b,_randomized,_placebo_controlled,.4.aspx
  24. Cano A, Nappi RE, Santoro N, et al. Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials. BJOG. 2024 Feb 6 PMID: 38320967 Free article
  25. Pinkerton JV, Simon JA, Joffe H et al Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause. OASIS 1 and 2 Randomized Clinical Trials. JAMA. Published online August 22, 2024. PMID: 39172446 https://jamanetwork.com/journals/jama/fullarticle/2822766